The cardiovascular and respiratory responses to dynamic exercise are well established and include increases in sympathetic discharge to the vasculature, increases in heart rate and contractility, as well as increases in breathing frequency and tidal volume. A reflex arising from exercising muscles is believed to be partly responsible for these effects. The overall aim of the experiments proposed in this application is to determine the exercise-induced mechanical and metabolic stimuli to thin fiber muscle afferents (i.e., group III and IV) that evoke these reflex autonomic and ventilatory adjustments. Dynamic exercise will be induced in decerebrate unanesthetized cats by electrical and possibly chemical stimulation of the mesencephalic locomotor region. Mechanogated channels will be blocked by gadolinium. Likewise, metabolic stimuli will focus on cyclooxygenase products of arachidonic acid, bradykinin and the purines. Indomethacin and similar acting agents will be used to block cyclooxygenase activity. HOE-140 will be used to block bradykinin-2 receptors, and CGS-15943 and PPADS will be used to block Purinergic 1 and 2 receptors, respectively. The effects of these "blocking agents" on thin fiber afferent discharge during dynamic exercise will be examined both when the working triceps surae muscles are freely perfused and when their circulation is occluded. Particular attention will be paid to the period of post-exercise circulatory occlusion, which is a pure metaboreceptor stimulus. The proposed studies should shed new light on the roles played by mechanical and metabolic stimuli in stimulating the group III and IV muscle afferents that in turn evoked the exercise pressor reflex. [unreadable] [unreadable]